A large number of pulmonary and aerodigestive tract disorders, ranging from aspiration pneumonitis, and lung abscesses to benign inflammatory lesions of the larynx and aerodigestive tract are caused by misdirection of gastric content into the respiratory system. The mechanisms of airway protection during retrograde transit of gastric content through the esophagopharyngeal lumen is not completely understood. In addition, although substantial information is available regarding the volume clearance of the aspirated material by the pulmonary structures, the defense mechanisms of the alveolar and bronchial linings against aspirated gastric acid remains unclear. Because of multisystem/organ involvement, systematic investigation of these mechanisms in health and disease conditions requires expertise from multiple disciplines. For this reason, during the past three years a concerted multidisciplinary, multidepartmental effort with participation of investigators from the Departments of Medicine, Otolaryngology, and Radiology was organized at the Medical College of Wisconsin Dysphagia Institute to systematically address these issues. The long-term objective of this program project is to provide the basis for preventive and/or therapeutic interventions in the future through the understanding of the central neural control and peripheral protective mechanisms against retrograde aspiration. All of the projects in this program share the common interest of identifying, characterizing, and quantitating the mechanisms that contribute to the protection of the airway against aspiration of gastric content in health and disease. The theme of this program project grant encompasses the function of the gastroesophageal junction as it relates to escape of gastric content into the esophagus, the significance of esophagopharyngeal, esophagolaryngeal, and pharyngolaryngeal reflexes in the closure mechanism of the tracheal inlet in response to gastroesophageal and esophagopharyngeal reflux and vomiting, and the role of bronchoalveolar defense mechanisms against acid alkaline and water exposure. The proposed program includes four projects and the administrative core. Projects 1 and 2 address the issue of extrapulmonary defense mechanisms against retrograde aspiration. Project 3 addresses the intrapulmonary defense mechanism against aspirated gastric content. Project 4 examines the mechanisms of airway protection during vomiting.